Does breast cancer start in the womb?

Perturbations in the foetal environment predispose individuals to diseases that become apparent in adulthood. These findings prompted researchers to hypothesize that foetal exposure to environmental oestrogens may play a role in the increased incidence of breast cancer observed in European and US populations over the last 50 years. There is widespread human exposure to bisphenol A, an oestrogenic compound that leaches from dental materials and consumer products. In CD-1 mice, perinatal exposure to environmentally relevant bisphenol A levels induced alterations of the mammary gland architecture. Bisphenol A increased the number of terminal end buds at puberty and terminal ends at 6 months of age and increased ductal lateral branching at 4 months of age. Exposed mice also showed an enhanced sensitivity to oestradiol when ovariectomized prior to puberty. All these parameters are associated in human beings with an increased risk for developing breast cancer. To assess whether bisphenol A induces mammary gland neoplasia, we chose a rat model because it more closely mimics the human disease than mouse models. Examination of the mammary glands of Wistar/Furth rats during early adulthood revealed that gestational exposure to bisphenol A induced the development of pre-neoplastic lesions and carcinoma in situ in the absence of any additional treatment aimed at increasing tumour development. Emerging epidemiological data reveal an increased incidence of breast cancer in women exposed to diethylstilboestrol during gestation. Hence, both animal experiments and epidemiological data strengthen the hypothesis that foetal exposure to xenooestrogens may be an underlying cause of the increased incidence of breast cancer observed over the last 50 years.